The murine misty mutation: phenotypic effects on melanocytes, platelets and brown fat.
Although the recessive murine mutation misty (m) is well known, its phenotype has never been reported beyond brief descriptions of a dilution of coat color and white spotting of the belly and extremities, suggesting a developmental mutation. A report in abstract has also suggested effects on white fat and body weight. Here, we report effects of the homozygous misty mutation on an unusual combination of three cell types: melanocytes, platelets, and brown fat. Brown fat appeared to be completely absent from all expected locations in neonatal m/m mice. A prolonged bleeding time was observed; platelet count and platelet serotonin and ATP levels were normal, but the level of ADP in m/m platelets was low. Primary cultures and immortal lines of melanocytes from m/m mice showed several abnormalities. There was a marked deficiency in net proliferation, suggesting that the color dilution and spotting in vivo may result from reduced numbers of melanocytes and their precursors. m/m melanocytes were also hyperdendritic in morphology, overproduced melanin, and had deficient responses to the cAMP agonists cholera toxin and melanocyte-stimulating hormone, which normally promote melanin production. The misty gene product may be involved in adenine nucleotide metabolism or signaling.
Sviderskaya
E V
EV
Department of Anatomy and Developmental Biology, St. George's Hospital Medical School, London, UK.
Novak
E K
EK
Swank
R T
RT
Bennett
D C
DC
D000255:Adenosine Triphosphate / Q000378:metabolism; D002001:Adipose Tissue, Brown / Q000002:abnormalities*; D000818:Animals; D001760:Bleeding Time; D001792:Blood Platelets / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects / Q000235:genetics; D005796:Genes / Q000235:genetics*; D006200:Hair Color / Q000235:genetics*; D008544:Melanocytes / Q000166:cytology* / Q000187:drug effects; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D009154:Mutation; D010641:Phenotype; D010670:Phenylthiourea / Q000494:pharmacology; D010858:Pigmentation / Q000235:genetics
D010670:Phenylthiourea; D000255:Adenosine Triphosphate